This invention relates to a novel composition of matter (hereinafter called interferon epsilon or interferon E) useful, for example, in human epithelial cell cultures as an anti-viral agent, to processes for producing the material, and to processes for treating human epithelial cells so as to resist viral infection.
Interferons are materials which have antiviral properties. They are produced by certain types of cells which have been stimulated by exposure to a virus, certain nucleic acids, or antigen/mitogen complexes. Interferons are extremely potent drugs which show great promise as clinical antiviral and anti-tumor agents.
There are currently three known types of human interferon: interferon alpha, produced from human leukocytes or lymphoblastoid cells; interferon beta, produced from fibroblasts; and interferon gamma, produced from human T-lymphocytes. All three are secreted by the respective cells after the cells are stimulated by viruses or analogous challenges. Human interferons may be differentiated from each other by type-specific antibody reactions or protein sequencing.
In the past, the antiviral activity of each particular type of interferon has been measured by its ability to protect human fibroblast cells in culture. A conventional antiviral unit of interferon is that concentration which protects one-half the cells in a human fibroblast culture from challenge with Vesicular Stomatitis Virus at a standard concentration.
Antiviral activity has been detected in other cells of human and of animal origin. Interference in the multiplication of influenza virus was first detected by Issacs and Lindenmann (1957) in cultures of chicken chorioallantoic membrane. Another example is the Hela cell line which is a transformed cancer cell of epithelial (cervical) origin as reported by G. Gey et al. in Cancer Research, Vol. 12, pp. 264-265, 1952. Various transformed or neoplastic cell lines originally derived from human epithelial tissue can be stimulated to produce interferon. See "Production of Interferon by Human Tumor Cell Lines", Jameson et al, Archives of Virology 62, 209-219 (1979).
In U.S. patent application Ser. No. 397,610, now abandoned, the present applicants disclosed the existence of a new material, called interferon epsilon, and described a method of producing it. As described in that application, an epithelial cell culture of human epidermal origin (keratinocytes) was grown and challenged to produce interferon. The interferon was secreted by the cells into the culture medium and subsequently partially purified by affinity chromatography. The interferon thus purified was shown to demonstrate characteristics distinct from the known alpha, beta, and gamma interferons.